Creatine is recognised as a dietary supplement capable of increasing muscle mass and muscle performance. It is provided in a number of different forms, but the main form is a creatine monohydrate, provided as a powder.
The ergogenic effect of Creatine has been a subject of systematic investigation since the late 1970's. To date, more than 300 sport-related studies have been performed, some 80% of these studies demonstrated significant positive effects of creatine on muscle mass, muscle power, lean body mass and performance at maximum, short duration muscle exertion in various types of sports. Today, creatine monohydrate is the most significant nutrition supplement in the field of sports.
A popular form of Creatine Monohydrate is CREAPURE™ marketed by AlzChem as a power supplement. The instructions that accompany the product recommend that the powder is added to a warm drink at a dose of 1 g per 100 mls. This means that in order to ingest the recommended dose of 3 g per day, a user will have to ingest 300 mls (at least) of a warm drink. In addition, the literature for the product indicates that the powder has no long term stability in water, which means that the product must be made up shortly before it is ingested (<10 minutes) and cannot be stored during the day.
In addition to creatine itself, namely creatine monohydrate, numerous creatine salts such as creatine ascorbate, citrate, pyruvate and others have in the meantime likewise proved to be suitable nutritional supplements. European patent EP 894 083 and German published patent application DE 197 07 694 A1 may be mentioned as representative prior art at this point.
Uptake of creatine from the intestine and transport into the muscles is controlled by an NaCl-dependent creatine transporter and may be promoted by the simultaneous intake of carbohydrates and proteins. It has therefore been found that in comparison with sole intake of creatine, the combination of creatine and carbohydrates can lead to a 60% greater rise in creatine content in the muscle (Green A. L., Hultman E., Macdonald I. A., Sewell D. A., Greenhaff P. L. Carbohydrate ingestion augments skeletal muscle creatine accumulation in during creatine supplementation in humans. Am J. Physiol. 1996 November; 271 (5 Pt 1): E821-6). Further formulations have been suggested to improve creatine uptake into the body. Patent application DE 10 2006 050 931.5 accordingly describes a solid or aqueous alkaline preparation comprising a creatine component, which contains a buffer system which establishes a pH value of 8.0-12.0.
US 2003215506 claims a formulation which enhances the creatine transport, said formulation containing IGF-1 modulating substance, in particular proteins, colostrum and recombinant IGF-1. Apart from its undisputed ergongenic and physiological effects, Creatine Monohydrate suffers from a number of limitations, including low solubility/hydration capacity and poor stability in aqueous solutions, and the fact that relatively large doses are required to elicit an ergogenic effect in the body. Since creatine does not have marked stability in water or corresponding aqueous solutions, creatine cyclising by elimination of water will generate creatinine. The rate of cyclisation is dependant on the pH value of the solution and the temperature. Intestinal concentration does not play any role in this process. Conversion to creatinine proceeds rapidly in particular in the acidic pH range between 3 and 4. The rapid break-down of creatinine in this medium virtually rules out the use of aqueous or moist formulations for human and animal nutrition. For example, based on the stomach pH alone, a significant breakdown of creatine to creatinine can occur depending on the residence time. (Greenhaff, P. L.: Factors Modifying Creatine Accumulation in Human Skeletal Muscle. In: Creatine. From Basic Science to Clinical Application. Medical Science Symposia Series Volume 14, 2000, 75-82).
The stated disadvantages of the prior art with regard to creatine solubility and stability in aqueous solution and subsequent uptake from the intestine and transport into the target tissue, give rise to the object of the present invention of providing encapsulated preparations of creatine, which better protect creatine than previously demonstrated. In this way, breakdown of creatine to creatinine can be avoided and lead to improved creatine uptake from the intestine. Hence, it is an object of the invention to overcome at least one of the above-referenced problems.
One vital factor, however, is the optimum uptake and thus retention of the creatine in the target tissue. A further object of the invention was to ensure that the creatine absorbed from the intestine is optimally taken up into the target tissue and is not excreted as such via the kidneys or converted into creatinine, which is useless to the body and must likewise be excreted from the body via the kidneys. Therefore the encapsulated systems have acceptable organoleptic properties with improved bioavailability for food and beverage applications.
The majority of creatine in the human body is in two forms, either the phosphorylated form making up 60% of the stores or in the free form which makes up 40% of the stores. The average 70 kg young male has a creatine pool of around 120-140 g which varies between individuals depending on the skeletal muscle fiber type and quantity of muscle mass. The endogenous production and dietary intake matches the rate of creatinine production from the degradation of phosphocreatine and creatine at 2.6% and 1.1%/d respectively. In general, oral creatine supplementation leads to an increase of creatine levels within the body. Creatine can be cleared from the blood by saturation into various organs and cells or by renal filtration.
Three amino acids (glycine, arginine and methionine) and three enzymes (L-arginine: glycine amidinotransferase, guanidinoacetate methyltransferase and methionine adenosyltransferase) are required for creatine synthesis. The impact creatine synthesis has on glycine metabolism in adults is low, however the demand is more appreciable on the metabolism of arginine and methionine.
Creatine ingested through supplementation is transported into the cells exclusively by CreaT1. However, there is another creatine transporter Crea T2, which is primarily active and present in the testes. Creatine uptake is regulated by various mechanisms, namely phosphorylation and glycosylation as well as extracellular and intracellular levels of creatine. Crea T1 has shown to be highly sensitive to the extracellular and intracellular levels being specifically activated when total creatine content inside the cell decreases. It has also been observed that in addition to cytosolic creatine, the existence of a mitochondrial isoform of Crea T1 allows creatine to be transported into the mitochondria. Indicating another intra-mitochondrial pool of creatine, which seems to play an essential role in the phosphate-transport system from the mitochondria to the cytosol. Myopathy patients have demonstrated reduced levels of total creatine and phosphocreatine as well as lower levels of CreaT1 protein, which is thought to be a major contributor to these decreased levels.
It is an object of the invention to overcome at least one of the above-referenced problems.